22-32686057-G-A

Variant names:

• chr22-32686057-G-A
• rs5998577
• NM_003490.4:c.712-89321C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.712-89321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,044 control chromosomes in the GnomAD database, including 2,513 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2513 hom., cov: 32)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 1 publications found

Genes affected

SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003490.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	NM_003490.4	MANE Select	c.712-89321C>T		intron	N/A	NP_003481.3
	SYN3	NM_001369907.1		c.712-89321C>T		intron	N/A	NP_001356836.1
	SYN3	NM_001369908.1		c.712-89321C>T		intron	N/A	NP_001356837.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYN3	ENST00000358763.7	TSL:5 MANE Select	c.712-89321C>T		intron	N/A	ENSP00000351614.2
	SYN3	ENST00000462268.1	TSL:3	n.226-56189C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27067 AN: 151926 Hom.: 2513 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27078 AN: 152044 Hom.: 2513 Cov.: 32 AF XY: 0.178 AC XY: 13219 AN XY: 74324

African (AFR) AF: 0.117 AC: 4863 AN: 41488

American (AMR) AF: 0.169 AC: 2583 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1150 AN: 5166

South Asian (SAS) AF: 0.268 AC: 1289 AN: 4818

European-Finnish (FIN) AF: 0.176 AC: 1854 AN: 10562

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13906 AN: 67958

Other (OTH) AF: 0.173 AC: 365 AN: 2110

Alfa AF: 0.204 Hom.: 1683

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5998577; hg19: chr22-33082043;